10.1002/chem.202002896
Chemistry - A European Journal
COMMUNICATION
1,3-dipolar cycloadditions of diaryl nitrile imines are not always
completely concerted, and that the electronic nature of the C-
aryl ring of the tetrazole may influence the rate of
decomposition.[32-33] This hypothesis could also explain the lower
yield obtained for the electron-rich thiophene-containing
oxadiazole 5k, while electron-poor substrates were generally
obtained in higher yields.
Acknowledgements
We thank the EPSRC for funding via Prosperity Partnership
EP/S035990/1, and gratefully acknowledge financial support
from GlaxoSmithKline R&D Ltd.
Keywords: Flow • heterocycles • Huisgen reaction • nitrile
imines • photochemistry
5-substituted alkyl tetrazoles were examined, however, only
the cyclopropyl oxadiazole 5d was formed in significant
quantities. Figure 1 indicates additional substrates where very
little or no reaction was observed. This may be due to a shift in
the maximum wavelength of absorption (λmax) of the tetrazoles,
due to the presence of alkyl rather than aromatic groups. As
such, the energy of UV-B light may not be sufficient to enable
formation of the nitrile imine and therefore the oxadiazole. The
successful formation of oxadiazole 5d may be attributed to the
interaction between the π-like orbitals of the cyclopropyl ring[34]
with those of the tetrazole, which may lower the λmax in an
analogous manner to an aromatic substituent.
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traditional thermolytic process. When incorporated into a simple
flow chemistry manifold, this method is amenable to scale up,
and enables the synthesis of a broad palette of valuable
oxadiazole analogues from readily available precursors in a
highly efficient manner. This represents
advancement in the light-mediated synthesis of this
fundamentally important heterocyclic template.
a
significant
4
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